Associations of C‐Reactive Protein‐Triglyceride Glucose Index and Estimated Pulse Wave Velocity With All‐Cause Mortality: A Nationwide Prospective Cohort Study

ABSTRACT Background and Aims The combined prognostic value of metaflammation and vascular aging markers in cardiovascular‐kidney‐metabolic (CKM) syndrome is unclear. This study aimed to assess the independent and joint associations of the C‐reactive protein‐triglyceride glucose index (CTI) and estimated pulse wave velocity (ePWV) with all‐cause mortality. Methods This prospective study included 7183 participants from the CHARLS 2011 survey (original cohort) and 9594 from 2015 (temporal sensitivity analysis cohort). Multivariable Cox models and restricted cubic splines were used. Joint effects were analyzed by median‐based groups, and mediation was tested using the KHB method. Results During follow‐up, 906 deaths occurred in the original cohort. Each 1‐unit increase in CTI was associated with a 56% higher mortality risk (HR = 1.56, 95% CI: 1.37–1.77), and each 1 m/s increase in ePWV with an 11% higher risk (HR = 1.11, 95% CI: 1.05–1.18). The high CTI/high ePWV group had the highest risk (HR = 1.73, 95% CI: 1.31–2.29). ePWV mediated 6.48% of the CTI‐mortality association, while CTI mediated 2.62% of the ePWV‐mortality association. These findings were confirmed in the temporal sensitivity analysis. Conclusion CTI and ePWV independently and jointly associate with increased all‐cause mortality. The observed bidirectional mediation suggests potentially interconnected pathways that warrant further investigation. Integrating these accessible biomarkers could improve risk stratification in CKM syndrome.